Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek’s disease virus

• Main Authors: Matsuyama-Kato Ayumi, Murata Shiro, Isezaki Masayoshi, Kano Rika, Takasaki Sara, Ichii Osamu, Konnai Satoru, Ohashi Kazuhiko
• Format: Article
• Language: English
• Published: BMC 2012-05-01
• Series: Virology Journal
• Online Access: http://www.virologyj.com/content/9/1/94

<p>Abstract</p> <p>Background</p> <p>An immunoinhibitory receptor, programmed death-1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), are involved in immune evasion mechanisms for several pathogens causing chronic infections and for neoplastic diseases. However, little has been reported for the functions of these molecules in chickens. Thus, in this study, their expressions and roles were analyzed in chickens infected with Marek’s disease virus (MDV), which induces immunosuppression in infected chickens.</p> <p>Results</p> <p>A chicken T cell line, Lee1, which constitutively produces IFN-γ was co-cultured with DF-1 cells, which is a spontaneously immortalized chicken fibroblast cell line, transiently expressing PD-L1, and the <it>IFN-γ</it> expression level was analyzed in the cell line by real-time RT-PCR. The <it>IFN-γ</it> expression was significantly decreased in Lee1 cells co-cultured with DF-1 cells expressing PD-L1. The expression level of <it>PD-1</it> was increased in chickens at the early cytolytic phase of the MDV infection, while the <it>PD-L1</it> expression level was increased at the latent phase. In addition, the expression levels of <it>PD-1</it> and <it>PD-L1</it> were increased at tumor lesions found in MDV-challenged chickens. The expressions levels of <it>PD-1</it> and <it>PD-L1</it> were also increased in the spleens and tumors derived from MDV-infected chickens in the field.</p> <p>Conclusions</p> <p>We demonstrated that the chicken PD-1/PD-L1 pathway has immunoinhibitory functions, and PD-1 may be involved in MD pathogenesis at the early cytolytic phase of the MDV infection, whereas PD-L1 could contribute to the establishment and maintenance of MDV latency. We also observed the increased expressions of <it>PD-1</it> and <it>PD-L1</it> in tumors from MDV-infected chickens, suggesting that tumor cells transformed by MDV highly express PD-1 and PD-L1 and thereby could evade from immune responses of the host.</p>